Learnings from the First 10 years the Paediatric Regulation- Back to inform on the Future?
20.04.18
A summary from a DIA Europe session by Heidrun Hildebrand, Global Program Head, Bayer; Angelika Joos, Executive Director, Global Regulatory Policy, MSD; Silvia Garcia, Senior Manager, Regulatory, Drug development and Manufacturing
Speakers of the session were Simon Bennett (Biogen), Heidrun Hildebrand (Bayer AG), Florian Schmidt ( DG Sante, EC) and Mark Turner (Senior Lecturer in Neonatology)
It was agreed by all speakers (regulators, industry and academia) that Paediatric regulation is a success.
The 10 years' Paediatric Report published end of 2017 by European Commision included an analysis of the economic impact of the rewards and incentives together with an analysis of the estimated consequences for public health of this Regulation, with a view to proposing any necessary amendments.
Regulation has been successful as the proportion of clinical trials that include children has increased by 50% in 2007-2016 (from 8.25% to 12.4% of all trials conducted in the EU).
260 new medicines for children were authorised between 2007 and 2016. It was indicated that the number of PIPs as a first step in developing medicines for children was > 1000 in 2017. 131 PIPs were completed at the end of 2016 and over 60% were finalised in the last 3 years. Given the in general long development timelines, these indicates that the regulation is working and results in new medicines in the end.
However, the regulation does not work well for Orphan products used in children due to lack of eligible patients for clinical trials and does not foster "mechanism of action"driven development (developments based on the way the products works independent of the adult indication) in Oncology, although this is allowed under the current law.
The challenges to overcome still are: the differences in development activity based on scientific maturity level between the various therapeutic areas, the overlaps with the orphan legislation that are blurring the boundaries and the timely completion of PIPs to enable the rewards that are not always "working".
A pragmatic approach can be the " iterative PIP". The initial PIP will be filled early, as per the regulation, but will use sequential submissions to build an iterative PIP that will include more and more details and progressively modify the agreed elements informed through newly available data from the development activity.
With regards to the more practical challenges related to initiation and conduct of clinical trials in children one of the key issues are the very heterogeneous landscape of national regulations supporting the conduct of such studies in the different EU member states, and secondly the fact that the infrastructure (site, investigators etc.) needed to perform such studies are not build with the same pace as the number of increasing studies would mandate. Improvement of this situation is expected from a more consistent implementation of the new clinical trials directive across all European member states and from different initiatives to improve related trial infrastructure.
Paediatric needs, scientific opportunity and commercial potential are guiding the development activity in innovative Industry. Establishing the paediatric needs is therefore essential to directing more scientific research into disease epidemiology and molecular understanding, biomarkers and paediatric endpoint development that will be needed to enable the medicine development moving forward. The planning of clinical trials should start early and including a better design to reduce the inherent uncertainties and risks around development.
Small population available to conduct clinical trials in rare diseases provide huge operational and logistical challenges.
With the arrival of the digital health tools to measure outcomes ( eg wearables) as well as modelling and simulation methodologies may provide new opportunities for smarter programs.
Fragmentation of reimbursement rules in Europe and value assessment for paediatric medicines remains an issue.
Next steps are to involve multi-stakeholders in better identifying paediatrics needs, analysing the grounds for use of deferrals, investing in research infrastructure and identifying bottlenecks to speedier completion of PIPs, analyse the handling of PIP applications and if necessary adapt guidelines.
To provide additional transparency and better information on new products authorised with paediatric indications the EMA will deliver regular updates about development and trends of the paediatrics medicines. They will also foster international cooperation and harmonisation.
Timely action to move forward is important because there are only 2 years time to evaluate the situation: the Commission is currently conducting a study to investigate the specific situation for orphans and a final evaluation of the system is expected by 2019. Industry, the Commission and other stakeholders are agreeing that the only way to progress the current situation is to bringing different stakeholders together to collaboratively work on eliminating the identified hurdles (eg Paediatrics EMA multi-stakeholder workshop on 20th March 2018).